Microscopy has developed to the state where it can complement X-ray crystallography and multidimensional NMR by determining the spatial distribution of labeled proteins and nucleic acids in cells and sub-cellular components. Especially powerful are new methods that allow correlating observations made by laser scanning confocal or multi-photon microscopy directly with intermediate high-voltage electron microscope (IVEM). The purpose of the Microscopy Core is to provide excellent facilities and the expertise to enable all members of this program to apply state-of-the-art microscopy techniques with little need for prior experience with microscopy methods. For suitable imaging studies, the Microscopy Core will have access to the extensive facilities and highly knowledgeable staff of the National Center for Microscopy and Imaging Research at San Diego (NCMIR). The unique capabilities developed or improved at NCMIR include: (1) Fluorescence photo-oxidation, which has proven to be a valuable tool for studying the three-dimensional (3-D) organization of cellular constituents by confocal microscopy and intermediate high-voltage electron microscopy. (2) Electron tomography, which can explore the 3-D distribution of components of kinase anchoring proteins and associated supramacromolecular and cellular components. (3) Multi-protein labeling (sometimes called multicolor), in which the distribution of several proteins can be simultaneously observed by confocal microscopy using two or more molecular species of fluorophores with different excitation and emission wavelengths and labeling agents. (4) Several software packages which are critical for the visualization and interpretation of structural information derived from microscope images.